Selective cd8-positive t cell-inducing vaccine antigen

Abstract

The present invention provides polypeptides for selectively inducing target antigen-specific CD8-positive T-cell responses. Since induction of human immunodeficiency virus (HIV)-specific CD4-positive T-cell responses by vaccine could promote HIV infection, an HIV vaccine antigen that selectively induces HIV-specific CD8-positive T-cell responses would be useful if obtained. Thus, in the present invention, polypeptide antigens were designed in which 8- to 12-residue amino acid sequences divided from the amino acid sequence of a target antigen protein were connected in an order different from that of the original amino acid sequence. DNA and viral vector vaccines expressing these antigens were tested by inoculation into monkeys. As a result, they were shown to be able to efficiently induce antigen-specific CD8-positive T-cell responses in a selective manner. The instant antigens may be useful as vaccine antigens that induce CD8-positive T cells in a highly selective manner.

1 . A polypeptide comprising multiple peptides connected together, wherein each of the multiple peptides has an amino acid sequence of eight to twelve residues included in the amino acid sequence of an antigen protein. 
     
     
         2 . The polypeptide of  claim 1 , wherein the eight- to twelve-residue peptides are connected in an order different from that in the antigen protein. 
     
     
         3 . The polypeptide of  claim 1  or  2 , which does not substantially comprise a partial amino acid sequence of 13 or more consecutive residues in the antigen protein. 
     
     
         4 . The polypeptide of any one of  claims 1  to  3 , wherein the amino acid sequences of the multiple peptides optionally comprise an overlap. 
     
     
         5 . The polypeptide of  claim 4 , wherein the overlap consists of one to four residues. 
     
     
         6 . The polypeptide of any one of  claims 1  to  5 , wherein each of the connection sites optionally comprises a spacer. 
     
     
         7 . The polypeptide of  claim 6 , wherein the spacer consists of one to four amino acid residues. 
     
     
         8 . The polypeptide of any one of  claims 1  to  7 , wherein at least 20 eight- to twelve-residue peptides are connected together. 
     
     
         9 . A nucleic acid encoding the polypeptide of any one of  claims 1  to  8 . 
     
     
         10 . A vector comprising the nucleic acid of  claim 9 . 
     
     
         11 . The vector of  claim 10 , which is a Sendai virus vector. 
     
     
         12 . A vaccine comprising the polypeptide of any one of  claims 1  to  8 , a nucleic acid encoding the polypeptide, or a vector comprising the nucleic acid. 
     
     
         13 . The vaccine of  claim 12 , wherein the antigen protein is derived from an antigen protein of a human immunodeficiency virus. 
     
     
         14 . A method for selectively inducing CD8-positive T cells specific for a target antigen, which comprises inoculating the vaccine of  claim 12  or  13 . 
     
     
         15 . A method for producing the polypeptide of  claim 1  or a nucleic acid encoding the polypeptide, which comprises:
 (i) dividing an amino acid sequence encoding an antigen protein into amino acid sequences of eight to twelve residues, wherein the divided amino acid sequences may or may not overlap with one another; 
 (ii) connecting the divided amino acid sequences in such a way as not to become the same as the amino acid sequence of the antigen protein, wherein a spacer may or may not be inserted in each of the connection sites of the divided amino acid sequences; and 
 (iii) obtaining a polypeptide comprising an amino acid sequence resulting from step (ii) or a nucleic acid encoding the polypeptide.